Modified Vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus that cannot replicate in human cells. This project include two clinical trials, which were phase I/II, randomized, placebo-controlled, double-blinded, schedule-finding studies of MVA. VRC 201 enrolled healthy young adults who were vaccinia-naive, and VRC 203 enrolled healthy adults who were vaccinated against smallpox more than 10 years ago. Subjects were randomized to different primary immunization schedules either with Dryvax or with MVA or placebo. Each schedule included a Dryvax challenge 12 weeks after completion of the primary vaccination schedule. Safety evaluations were performed on an ongoing basis throughout the studies and immunogenicity samples were collected and frozen for batch testing by research laboratories. VRC 201 was closed to accrual in June 2004 with 77 of the target 105 subjects enrolled and VRC 203 was closed to accrual in June 2004 with 75 of the target 80 subjects enrolled. In FY 06 the final safety and immunogenicity analysis was completed. In addition, a collaboration with Genoveffa Franchini occurred in which ELISA assays developed for the human protocol were applied to NHP studies from her laboratory.